Mechanisms of ZnII-activated magnetic resonance imaging agents.
We report on the mechanism of a series of Zn (II)-activated magnetic resonance contrast agents that modulate the access of water to a paramagnetic Gd (III) ion to create an increase in relaxivity upon binding of Zn (II). In the absence and presence of Zn (II), the coordination at the Gd (III) center is modulated by appended Zn (II) binding groups. These groups were systematically varied to optimize the change in coordination upon Zn (II) binding. We observe that at least one appended aminoacetate must be present as a coordinating group to bind Gd (III) and effectively inhibit access of water. At least two binding groups are required to efficiently bind Zn (II), creating an unsaturated complex and allowing access of water. (13)C isotopic labeling of the acetate binding groups for NMR spectroscopy provides evidence of a change in the metal coordination of these groups upon the addition of Zn (II) supporting our proposed mechanism of activation as presented.
Major
Jody L
JL
Department of Chemistry, Biochemistry and Molecular Cell Biology, Neurobiology and Physiology, and Radiology, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208-3113, USA.
Boiteau
Rene M
RM
Meade
Thomas J
TJ
D002413:Cations, Divalent / Q000737:chemistry; D003287:Contrast Media / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry*; D005998:Glycine / Q000737:chemistry; D047028:Macrocyclic Compounds / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009942:Organometallic Compounds / Q000737:chemistry*; D014867:Water / Q000737:chemistry; D015032:Zinc / Q000737:chemistry*
D002413:Cations, Divalent; D003287:Contrast Media; D047028:Macrocyclic Compounds; D009942:Organometallic Compounds; D014867:Water; D005682:Gadolinium; D015032:Zinc; D005998:Glycine